Is GRID2 p.Gly417= (c.1251T>G) pathogenic?

GRID2 p.Gly417= (c.1251T>G) is classified Benign in GRID2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 92.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive spinocerebellar ataxia 18.

What condition is associated with GRID2 p.Gly417= (c.1251T>G)?

GRID2 p.Gly417= (c.1251T>G) is associated with autosomal recessive spinocerebellar ataxia 18 (ClinVar).

GRID2 p.Gly417=

Q: How common is GRID2 p.Gly417= (c.1251T>G) in the general population?

GRID2 p.Gly417= (c.1251T>G) is common (popmax 92.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1251T>G · rs1385405 · VCV1266413

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 92.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive spinocerebellar ataxia 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.86	GERP -4.2
Overall
CADD	5.319	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 92.6% African / African-American · 66,309/71,580 alleles

Filtering AF 92% ClinGen BA1/BS1 input FAF95, joint · FAF99 91.8%

Overall 64.4% 950,225/1,474,840 alleles · common exomes 840,988/1,322,990 · genomes 109,237/151,850 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	92.6%	1
East Asian	73.6%	1
Middle Eastern	73.2%	1
South Asian	72.8%	1
Finnishnot grpmax-eligible	67.8%	1
Remaining individualsnot grpmax-eligible	66.3%	2
Ashkenazi Jewishnot grpmax-eligible	62.7%	2
European (non-Finnish)	61.6%	2
Admixed American	55.8%	2
Amishnot grpmax-eligible	52.7%	2

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GRID2
Protein: p.Gly417=
Coding: c.1251T>G
MANE Select: NM_001510
dbSNP: rs1385405
Type: single nucleotide variant
Location: chr4:93395612 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB
Residue 417: a β-strand

Full GRID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive spinocerebellar ataxia 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GRID2 p.Thr649Ala Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Arg300His Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg367His Uncertain significance ★★ ⚠ same condition
GRID2 p.Asp473Glu Uncertain significance ★★ ⚠ same condition
GRID2 p.Gly391Arg Uncertain significance ★★ ⚠ same condition
GRID2 c.735+21G>C Benign ★★ same condition
GRID2 p.Arg224Gln Likely pathogenic ★ ⚠ same condition
GRID2 p.Gln190Ter Pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/grid2-p-gly417 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown